全文获取类型
收费全文 | 2892篇 |
免费 | 252篇 |
国内免费 | 4篇 |
出版年
2022年 | 26篇 |
2021年 | 63篇 |
2020年 | 38篇 |
2019年 | 49篇 |
2018年 | 49篇 |
2017年 | 43篇 |
2016年 | 78篇 |
2015年 | 106篇 |
2014年 | 129篇 |
2013年 | 158篇 |
2012年 | 162篇 |
2011年 | 194篇 |
2010年 | 108篇 |
2009年 | 104篇 |
2008年 | 115篇 |
2007年 | 133篇 |
2006年 | 121篇 |
2005年 | 96篇 |
2004年 | 123篇 |
2003年 | 99篇 |
2002年 | 119篇 |
2001年 | 35篇 |
2000年 | 25篇 |
1999年 | 29篇 |
1998年 | 21篇 |
1997年 | 23篇 |
1996年 | 24篇 |
1995年 | 22篇 |
1994年 | 16篇 |
1993年 | 16篇 |
1992年 | 14篇 |
1991年 | 18篇 |
1990年 | 21篇 |
1989年 | 26篇 |
1988年 | 21篇 |
1987年 | 22篇 |
1986年 | 23篇 |
1985年 | 15篇 |
1984年 | 33篇 |
1983年 | 23篇 |
1982年 | 31篇 |
1981年 | 23篇 |
1980年 | 33篇 |
1979年 | 14篇 |
1978年 | 15篇 |
1976年 | 15篇 |
1974年 | 14篇 |
1973年 | 24篇 |
1969年 | 14篇 |
1939年 | 13篇 |
排序方式: 共有3148条查询结果,搜索用时 46 毫秒
121.
122.
Environmental strain Burkholderia sp. DNT mineralizes the xenobiotic compound 2,4-dinitrotoluene (DNT) owing to the catabolic dnt genes borne by plasmid DNT, but the process fails to promote significant growth. To investigate this lack of physiological return of such an otherwise complete metabolic route, cells were exposed to DNT under various growth conditions and the endogenous formation of reactive oxygen species (ROS) monitored in single bacteria. These tests revealed the buildup of a strong oxidative stress in the population exposed to DNT. By either curing the DNT plasmid or by overproducing the second activity of the biodegradation route (DntB) we could trace a large share of ROS production to the first reaction of the route, which is executed by the multicomponent dioxygenase encoded by the dntA gene cluster. Naphthalene, the ancestral substrate of the dioxygenase from which DntA has evolved, also caused significant ROS formation. That both the old and the new substrate brought about a considerable cellular stress was indicative of a still-evolving DntA enzyme which is neither optimal any longer for naphthalene nor entirely advantageous yet for growth of the host strain on DNT. We could associate endogenous production of ROS with likely error-prone repair mechanisms of DNA damage, and the ensuing stress-induced mutagenesis in cells exposed to DNT. It is thus plausible that the evolutionary roadmap for biodegradation of xenobiotic compounds like DNT was largely elicited by mutagenic oxidative stress caused by faulty reactions of precursor enzymes with novel but structurally related substrates-to-be. 相似文献
123.
Aurélie Bedel Jean- Max Pasquet éric Lippert Miguel Taillepierre Valérie Lagarde Sandrine Dabernat Pierre Dubus Lucie Charaf Fran?ois Beliveau Hubert de Verneuil Emmanuel Richard Fran?ois-Xavier Mahon Fran?ois Moreau-Gaudry 《PloS one》2013,8(8)
Chronic myeloid leukemia disease (CML) found effective therapy by treating patients with tyrosine kinase inhibitors (TKI), which suppress the BCR-ABL1 oncogene activity. However, the majority of patients achieving remission with TKI still have molecular evidences of disease persistence. Various mechanisms have been proposed to explain the disease persistence and recurrence. One of the hypotheses is that the primitive leukemic stem cells (LSCs) can survive in the presence of TKI. Understanding the mechanisms leading to TKI resistance of the LSCs in CML is a critical issue but is limited by availability of cells from patients. We generated induced pluripotent stem cells (iPSCs) derived from CD34+ blood cells isolated from CML patients (CML-iPSCs) as a model for studying LSCs survival in the presence of TKI and the mechanisms supporting TKI resistance. Interestingly, CML-iPSCs resisted to TKI treatment and their survival did not depend on BCR-ABL1, as for primitive LSCs. Induction of hematopoietic differentiation of CML-iPSC clones was reduced compared to normal clones. Hematopoietic progenitors obtained from iPSCs partially recovered TKI sensitivity. Notably, different CML-iPSCs obtained from the same CML patients were heterogeneous, in terms of BCR-ABL1 level and proliferation. Thus, several clones of CML-iPSCs are a powerful model to decipher all the mechanisms leading to LSC survival following TKI therapy and are a promising tool for testing new therapeutic agents. 相似文献
124.
Vincent Daien Isabelle Carriere Ryo Kawasaki Jean-Paul Cristol Max Villain Pierre Fesler Karen Ritchie Cecile Delcourt 《PloS one》2013,8(7)
Purpose
Retinal vascular caliber has been linked with increased cardiovascular risk and is predictive of cardiovascular pathology, including stroke and coronary heart disease. Oxidative stress, as well as inflammatory mechanisms, plays a major role in the pathogenesis and progression of atherosclerosis, plaque rupture and vascular thrombotic propensity. The purpose of this study is to explore the relationship between retinal vascular calibers and biomarkers of oxidative stress and inflammation, in subjects free of cardiovascular pathology.Patients and Methods
Cross-sectional analysis from a community-dwelling cohort comprising 1224 individuals aged 60 years and over, without a history of coronary or peripheral artery disease or stroke. Retinal vascular caliber was measured from fundus photographs using semi-automated standardized imaging software. Oxidative stress was evaluated using plasma superoxide dismutase 2 and glutathione peroxidase (GPx-3) activities, and inflammatory state was assessed using plasma high sensitivity C-reactive protein (hsCRP) and orosomucoid.Results
In a multivariate model controlling for cardiovascular risk factors, larger retinal arteriolar caliber was independently related to higher level of GPx-3 activity (p = 0.003) whereas larger venular caliber was associated with higher levels of hsCRP (p = 0.0001) and orosomucoid (p = 0.01).Conclusion
In the present study, biomarkers of oxidative stress regulation and inflammation were independently associated with retinal vascular calibers. This suggests that an assessment of retinal vessels may offer early and non-invasive detection of subclinical vascular pathology. 相似文献125.
Environmental adaptation of crops is essential for reliable agricultural production and an important breeding objective. Genebanks provide genetic variation for the improvement of modern varieties, but the selection of suitable germplasm is frequently impeded by incomplete phenotypic data. We address this bottleneck by combining a Focused Identification of Germplasm Strategy (FIGS) with core collection methodology to select soybean (Glycine max) germplasm for Central European breeding from a collection of >17,000 accessions. By focussing on adaptation to high-latitude cold regions, we selected an “environmental precore” of 3,663 accessions using environmental data and compared the Donor opulation of Environments (DPE) in Asia and the Target Population of Environments (TPE) in Central Europe in the present and 2070. Using single nucleotide polymorphisms, we reduced the precore into two diverse core collections of 183 and 366 accessions to serve as diversity panels for evaluation in the TPE. Genetic differentiation between precore and non-precore accessions revealed genomic regions that control maturity, and novel candidate loci for environmental adaptation, demonstrating the potential of diversity panels for studying adaptation. Objective-driven core collections have the potential to increase germplasm utilization for abiotic adaptation by breeding for a rapidly changing climate, or de novo adaptation of crops to expand cultivation ranges. 相似文献
126.
Vanessa Julie Roden Imelda M. Hausmann Alexander Nützel Barbara Seuss Mike Reich Max Urlichs Hans Hagdorn Wolfgang Kiessling 《Palaeontology》2020,63(1):85-102
With 1429 animal species, the Triassic Cassian Formation in the Dolomites, Southern Alps (Italy), yields the highest species richness reported from any spatially constrained pre-Quaternary formation known to science. The high preserved diversity is partly attributable to a high primary diversity governed by the tropical setting, increasing alpha diversity, and the breadth of habitats spurring beta diversity. More important is the excellent preservation of fossils and the ease with which they can be extracted from the poorly lithified sediments. We propose the term ‘liberation Lagerstätten’ to capture this preservational window. In contrast to conservation Lagerstätten, liberation Lagerstätten like the Cassian Formation originate from normal marine conditions but low-grade diagenesis. Molluscs contribute substantially to species richness, comprising 67% of all invertebrate species in the Cassian Formation. The gastropod dominance (39% of all species) is nearly as great as in Recent tropical settings, contradicting the concept of a substantial Cenozoic rise. 相似文献
127.
128.
Max Beier 《New Zealand journal of zoology.》2013,40(3):199-246
Nearly 20 000 specimens of pseudoscorpions from a full range of habitats have been examined. For New Zealand, 70 species and subspecies in 28 genera are recognised, and for Norfolk and Lord Howe Islands, 11 species in 9 genera. Endemism is very high in this area: in New Zealand, 13 out of 25 indigenous genera are endemic; 2 others (Apatochernes, Nesochernes) are shared with Norfolk Island; and 4 (Sathrochthonius, Austrochthonius, Synsphyronus, Protochelifer) extend their distribution to Australia (Austrochthonius is known also from South America and South Africa). The rest of the native genera have a wider distribution in the Pacific. Three species (Lamprochernes savignyi, Withius subruber, Chelifer cancroides) have a wide and disjunct distribution induced by human traffic, and are considered to be an introduced element. 相似文献
129.
130.
Ana S. Luís Immacolata Venditto Max J. Temple Artur Rogowski Arnaud Baslé Jie Xue J. Paul Knox José A.M. Prates Luís M. A. Ferreira Carlos M. G. A. Fontes Shabir Najmudin Harry J. Gilbert 《The Journal of biological chemistry》2013,288(7):4799-4809
Plant biomass is central to the carbon cycle and to environmentally sustainable industries exemplified by the biofuel sector. Plant cell wall degrading enzymes generally contain noncatalytic carbohydrate binding modules (CBMs) that fulfil a targeting function, which enhances catalysis. CBMs that bind β-glucan chains often display broad specificity recognizing β1,4-glucans (cellulose), β1,3-β1,4-mixed linked glucans and xyloglucan, a β1,4-glucan decorated with α1,6-xylose residues, by targeting structures common to the three polysaccharides. Thus, CBMs that recognize xyloglucan target the β1,4-glucan backbone and only accommodate the xylose decorations. Here we show that two closely related CBMs, CBM65A and CBM65B, derived from EcCel5A, a Eubacterium cellulosolvens endoglucanase, bind to a range of β-glucans but, uniquely, display significant preference for xyloglucan. The structures of the two CBMs reveal a β-sandwich fold. The ligand binding site comprises the β-sheet that forms the concave surface of the proteins. Binding to the backbone chains of β-glucans is mediated primarily by five aromatic residues that also make hydrophobic interactions with the xylose side chains of xyloglucan, conferring the distinctive specificity of the CBMs for the decorated polysaccharide. Significantly, and in contrast to other CBMs that recognize β-glucans, CBM65A utilizes different polar residues to bind cellulose and mixed linked glucans. Thus, Gln106 is central to cellulose recognition, but is not required for binding to mixed linked glucans. This report reveals the mechanism by which β-glucan-specific CBMs can distinguish between linear and mixed linked glucans, and show how these CBMs can exploit an extensive hydrophobic platform to target the side chains of decorated β-glucans. 相似文献